An uncertainty-based interpretable deep learning framework for predicting breast cancer outcome.

BACKGROUND: Predicting outcome of breast cancer is important for selecting appropriate treatments and prolonging the survival periods of patients. Recently, different deep learning-based methods have been carefully designed for cancer outcome prediction. However, the application of these methods is still challenged by interpretability. In this study, we proposed a novel multitask deep neural network called UISNet to predict the outcome of breast cancer. The UISNet is able to interpret the importance of features for the prediction model via an uncertainty-based integrated gradients algorithm. UISNet improved the prediction by introducing prior biological pathway knowledge and utilizing patient heterogeneity information. RESULTS: The model was tested in seven public datasets of breast cancer, and showed better performance (average C-index = 0.691) than the state-of-the-art methods (average C-index = 0.650, ranged from 0.619 to 0.677). Importantly, the UISNet identified 20 genes as associated with breast cancer, among which 11 have been proven to be associated with breast cancer by previous studies, and others are novel findings of this study. CONCLUSIONS: Our proposed method is accurate and robust in predicting breast cancer outcomes, and it is an effective way to identify breast cancer-associated genes. The method codes are available at: https://github.com/chh171/UISNet .

AFEI: adaptive optimized vertical federated learning for heterogeneous multi-omics data integration.

Vertical federated learning has gained popularity as a means of enabling collaboration and information sharing between different entities while maintaining data privacy and security. This approach has potential applications in disease healthcare, cancer prognosis prediction, and other industries where data privacy is a major concern. Although using multi-omics data for cancer prognosis prediction provides more information for treatment selection, collecting different types of omics data can be challenging due to their production in various medical institutions. Data owners must comply with strict data protection regulations such as European Union (EU) General Data Protection Regulation. To share patient data across multiple institutions, privacy and security issues must be addressed. Therefore, we propose an adaptive optimized vertical federated-learning-based framework adaptive optimized vertical federated learning for heterogeneous multi-omics data integration (AFEI) to integrate multi-omics data collected from multiple institutions for cancer prognosis prediction. AFEI enables participating parties to build an accurate joint evaluation model for learning more information related to cancer patients from different perspectives, based on the distributed and encrypted multi-omics features shared by multiple institutions. The experimental results demonstrate that AFEI achieves higher prediction accuracy (6.5% on average) than using single omics data by utilizing the encrypted multi-omics data from different institutions, and it performs almost as well as prognosis prediction by directly integrating multi-omics data. Overall, AFEI can be seen as an efficient solution for breaking down barriers to multi-institutional collaboration and promoting the development of cancer prognosis prediction.

Integrating molecular interactions and gene expression to identify biomarkers to predict response to tumor necrosis factor inhibitor therapies in rheumatoid arthritis patients.

BACKGROUND: Targeted therapy using anti-TNF (tumor necrosis factor) is the first option for patients with rheumatoid arthritis (RA). Anti-TNF therapy, however, does not lead to meaningful clinical improvement in many RA patients. To predict which patients will not benefit from anti-TNF therapy, clinical tests should be performed prior to treatment beginning. OBJECTIVE: Although various efforts have been made to identify biomarkers and pathways that may be helpful to predict the response to anti-TNF treatment, gaps remain in clinical use due to the low predictive power of the selected biomarkers. METHODS: In this paper, we used a network-based computational method to identify the select the predictive biomarkers to guide the treatment of RA patients. RESULTS: We select 69 genes from peripheral blood expression data from 46 subjects using a sparse network-based method. The result shows that the selected 69 genes might influence biological processes and molecular functions related to the treatment. CONCLUSIONS: Our approach advances the predictive power of anti-TNF therapy response and provides new genetic markers and pathways that may influence the treatment.

Beyond the limitation of targeted therapy: Improve the application of targeted drugs combining genomic data with machine learning.

Precision oncology involves effectively selecting drugs for cancer patients and planning an effective treatment regimen. However, for Molecular targeted drug, using genomic state of the drug target to select drugs has limitations. Many patients who could benefit from molecularly targeted drugs, but they are being missed due to the insufficient labelling ability of the existing target genes. For non-specific chemotherapy drugs, most of the first-line anticancer drugs do not have biomarkers to guide doctor make treatment regimen. Furthermore, it is important to determine a long-term treatment plan based on the patient's genomic data during tumor evolution. Therefore, it is necessary to establish a tumor drug sensitivity prediction model, which can assist doctors in designing a personalized tumor treatment regimen. This paper proposed a novel model to predict tumor drug sensitivity including targeted drugs and non-specific chemotherapy drugs. This model uses statistical methods based on Bimodal distribution to select multimodal genetic data to solve dimensional challenges and reduce noise and to establish a classification model to predict the effectiveness of the drug in the tumor cell line using machine learning. The experimental test 87 molecular targeted drugs and non-specific chemotherapy drugs. The results show that the method can effectively predict the sensitivity of tumor drugs with an average sensitivity of 0.98 and specificity of 0.97. This model is worth to promotion. If it can be successfully used in clinical trials, it will effectively assist doctors to develop personalized cancer treatment programs and expand the application of molecularly targeted drugs.